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Current Opinion in Cell Biology Apr 2022In eukaryotes, there is now compelling evidence that in addition to the conventional endoplasmic reticulum-Golgi secretory pathway, there are additional routes for the... (Review)
Review
In eukaryotes, there is now compelling evidence that in addition to the conventional endoplasmic reticulum-Golgi secretory pathway, there are additional routes for the export of cytoplasmic proteins with a critical role in numerous physio-pathological conditions. These alternative secretory pathways or unconventional protein secretion (UPS) start now to be molecularly dissected, and while UPS landscape appears to be governed by a striking diversity and heterogeneity of mechanisms, common principles are emerging. We review here the role of key molecular determinants as well as the role of central hubs for UPS, highlighting the plasticity and dynamic properties of membrane-bound compartments. We also describe recent findings that position UPS as an integral component of adaptive responses to cope with particular cellular needs and stresses.
Topics: Endoplasmic Reticulum; Golgi Apparatus; Protein Transport; Proteins; Secretory Pathway
PubMed: 35305454
DOI: 10.1016/j.ceb.2022.02.006 -
Biology of the Cell Mar 2021Cell biology is evolving to become a more formal and quantitative science. In particular, several mathematical models have been proposed to address Golgi... (Review)
Review
BACKGROUND
Cell biology is evolving to become a more formal and quantitative science. In particular, several mathematical models have been proposed to address Golgi self-organisation and protein and lipid transport. However, most scientific articles about the Golgi apparatus are still using static cartoons that miss the dynamism of this organelle.
RESULTS
In this report, we show that schematic drawings of Golgi trafficking can be easily translated into an agent-based model using the Repast platform. The simulations generate an active interplay among cisternae and vesicles rendering quantitative predictions about Golgi stability and transport of soluble and membrane-associated cargoes. The models can incorporate complex networks of molecular interactions and chemical reactions by association with COPASI, a software that handles ordinary differential equations.
CONCLUSIONS
The strategy described provides a simple, flexible and multiscale support to analyse Golgi transport. The simulations can be used to address issues directly linked to the mechanism of transport or as a way to incorporate the complexity of trafficking to other cellular processes that occur in dynamic organelles.
SIGNIFICANCE
We show that the rules implicitly present in most schematic representations of intracellular trafficking can be used to build dynamic models with quantitative outputs that can be compared with experimental results.
Topics: Biological Transport; Golgi Apparatus; Humans
PubMed: 33275796
DOI: 10.1111/boc.202000107 -
Small GTPases Dec 2023Next year marks one-quarter of a century since the discovery of the so-called COPI-independent pathway, which operates between the Golgi apparatus and the endoplasmic... (Review)
Review
Next year marks one-quarter of a century since the discovery of the so-called COPI-independent pathway, which operates between the Golgi apparatus and the endoplasmic reticulum (ER) in eukaryotic cells. Unlike almost all other intracellular trafficking pathways, this pathway is not regulated by the physical accumulation of multisubunit proteinaceous coat molecules, but instead by the small GTPase Rab6. What also sets it apart from other pathways is that the transport carriers themselves often take the form of tubules, rather than conventional vesicles. In this review, we assess the relevant literature that has accumulated to date, in an attempt to provide a concerted description of how this pathway is regulated. We discuss the possible cargo molecules that are carried in this pathway, and the likely mechanism of Rab6 tubule biogenesis, including how the cargo itself may play a critical role. We also provide perspective surrounding the various molecular motors of the kinesin, myosin and dynein families that have been implicated in driving Rab6-coated tubular membranes long distances through the cell prior to delivering their cargo to the ER. Finally, we also raise several important questions that require resolution, if we are to ultimately provide a comprehensive molecular description of how the COPI-independent pathway is controlled.
Topics: Humans; HeLa Cells; Golgi Apparatus; Endoplasmic Reticulum; Coat Protein Complex I; Protein Transport
PubMed: 37488775
DOI: 10.1080/21541248.2023.2238330 -
Bioscience Reports May 2022Lysosomes are key regulators of many fundamental cellular processes such as metabolism, autophagy, immune response, cell signalling and plasma membrane repair. These... (Review)
Review
Lysosomes are key regulators of many fundamental cellular processes such as metabolism, autophagy, immune response, cell signalling and plasma membrane repair. These highly dynamic organelles are composed of various membrane and soluble proteins, which are essential for their proper functioning. The soluble proteins include numerous proteases, glycosidases and other hydrolases, along with activators, required for catabolism. The correct sorting of soluble lysosomal proteins is crucial to ensure the proper functioning of lysosomes and is achieved through the coordinated effort of many sorting receptors, resident ER and Golgi proteins, and several cytosolic components. Mutations in a number of proteins involved in sorting soluble proteins to lysosomes result in human disease. These can range from rare diseases such as lysosome storage disorders, to more prevalent ones, such as Alzheimer's disease, Parkinson's disease and others, including rare neurodegenerative diseases that affect children. In this review, we discuss the mechanisms that regulate the sorting of soluble proteins to lysosomes and highlight the effects of mutations in this pathway that cause human disease. More precisely, we will review the route taken by soluble lysosomal proteins from their translation into the ER, their maturation along the Golgi apparatus, and sorting at the trans-Golgi network. We will also highlight the effects of mutations in this pathway that cause human disease.
Topics: Child; Golgi Apparatus; Humans; Lysosomes; Protein Transport; Proteins
PubMed: 35394021
DOI: 10.1042/BSR20211856 -
Results and Problems in Cell... 2019Neurons forming the central nervous system are generated by neural stem and progenitor cells, via a process called neurogenesis (Götz and Huttner, Nat Rev Mol Cell... (Review)
Review
Neurons forming the central nervous system are generated by neural stem and progenitor cells, via a process called neurogenesis (Götz and Huttner, Nat Rev Mol Cell Biol, 6:777-788, 2005). In this book chapter, we focus on neurogenesis in the dorsolateral telencephalon, the rostral-most region of the neural tube, which contains the part of the central nervous system that is most expanded in mammals (Borrell and Reillo, Dev Neurobiol, 72:955-971, 2012; Wilsch-Bräuninger et al., Curr Opin Neurobiol 39:122-132, 2016). We will discuss recent advances in the dissection of the cell biological mechanisms of neurogenesis, with particular attention to the organization and function of the Golgi apparatus and its relationship to the centrosome.
Topics: Animals; Cell Polarity; Centrosome; Golgi Apparatus; Neural Stem Cells; Neuroepithelial Cells; Neurogenesis; Neurons
PubMed: 31435803
DOI: 10.1007/978-3-030-23173-6_15 -
Traffic (Copenhagen, Denmark) Aug 2023Deficiency in the conserved oligomeric Golgi (COG) complex that orchestrates SNARE-mediated tethering/fusion of vesicles that recycle the Golgi's glycosylation machinery...
Deficiency in the conserved oligomeric Golgi (COG) complex that orchestrates SNARE-mediated tethering/fusion of vesicles that recycle the Golgi's glycosylation machinery results in severe glycosylation defects. Although two major Golgi v-SNAREs, GS28/GOSR1, and GS15/BET1L, are depleted in COG-deficient cells, the complete knockout of GS28 and GS15 only modestly affects Golgi glycosylation, indicating the existence of an adaptation mechanism in Golgi SNARE. Indeed, quantitative mass-spectrometry analysis of STX5-interacting proteins revealed two novel Golgi SNARE complexes-STX5/SNAP29/VAMP7 and STX5/VTI1B/STX8/YKT6. These complexes are present in wild-type cells, but their usage is significantly increased in both GS28- and COG-deficient cells. Upon GS28 deletion, SNAP29 increased its Golgi residency in a STX5-dependent manner. While STX5 depletion and Retro2-induced diversion from the Golgi severely affect protein glycosylation, GS28/SNAP29 and GS28/VTI1B double knockouts alter glycosylation similarly to GS28 KO, indicating that a single STX5-based SNARE complex is sufficient to support Golgi glycosylation. Importantly, co-depletion of three Golgi SNARE complexes in GS28/SNAP29/VTI1B TKO cells resulted in severe glycosylation defects and a reduced capacity for glycosylation enzyme retention at the Golgi. This study demonstrates the remarkable plasticity in SXT5-mediated membrane trafficking, uncovering a novel adaptive response to the failure of canonical intra-Golgi vesicle tethering/fusion machinery.
Topics: Qa-SNARE Proteins; Golgi Apparatus; SNARE Proteins
PubMed: 37340984
DOI: 10.1111/tra.12903 -
Current Opinion in Cell Biology Aug 2020Virtually all transport events at the Golgi complex are regulated by Arf and Rab family GTPases. Recent work has advanced our knowledge regarding the mechanisms... (Review)
Review
Virtually all transport events at the Golgi complex are regulated by Arf and Rab family GTPases. Recent work has advanced our knowledge regarding the mechanisms controlling GTPase activity, and it has become clear that GTPases do not act in isolation but rather function in complex networks of crosstalk and feedback. Together with earlier findings, these recent studies indicate that communication between GTPases, their regulatory proteins, effectors, and lipids plays a pivotal role in Golgi transport and cisternal maturation.
Topics: Cell Membrane; GTP Phosphohydrolases; Golgi Apparatus; Humans; Models, Biological; Phosphorylation; Protein Transport
PubMed: 32143122
DOI: 10.1016/j.ceb.2020.01.014 -
Progress in Neurobiology Jun 2017The Golgi apparatus plays a central role in cell homeostasis, not only in processing and maturing newly synthesized proteins and lipids but also in orchestrating their... (Review)
Review
The Golgi apparatus plays a central role in cell homeostasis, not only in processing and maturing newly synthesized proteins and lipids but also in orchestrating their sorting, packing, routing and recycling on the way to their final destination. These multiple secretory pathways require a complex ballet of vesicular and tubular carriers that continuously bud off from donor membranes and fuse to acceptor membranes. Membrane trafficking is particularly prominent in axons, where cargo molecules have a long way to travel before they reach the synapse, and in oligodendrocytes, which require an immense increase in membrane surface in order to sheathe axons in myelin. Interestingly, in recent years, genes encoding Golgi-associated proteins with a role in membrane trafficking have been found to be defective in an increasing number of inherited disorders whose clinical manifestations include postnatal-onset microcephaly (POM), white matter defects and intellectual disability. Several of these genes encode RAB GTPases, RAB-effectors or RAB-regulating proteins, linking POM and intellectual disability to RAB-dependent Golgi trafficking pathways and suggesting that their regulation is critical to postnatal brain maturation and function. Here, we review the key roles of the Golgi apparatus in post-mitotic neurons and the oligodendrocytes that myelinate them, and provide an overview of these Golgi-associated POM-causing genes, their function in Golgi organization and trafficking and the likely mechanisms that may link dysfunctions in RAB-dependent regulatory pathways with POM.
Topics: Animals; Brain; Cell Membrane; Evidence-Based Medicine; Golgi Apparatus; Humans; Microcephaly; Models, Neurological; Protein Transport; rab GTP-Binding Proteins
PubMed: 28377289
DOI: 10.1016/j.pneurobio.2017.03.007 -
Archives of Pharmacal Research Oct 2022The Golgi apparatus is an essential cellular organelle that mediates homeostatic functions, including vesicle trafficking and the post-translational modification of... (Review)
Review
The Golgi apparatus is an essential cellular organelle that mediates homeostatic functions, including vesicle trafficking and the post-translational modification of macromolecules. Its unique stacked structure and dynamic functions are tightly regulated, and several Golgi proteins play key roles in the functioning of unconventional protein secretory pathways triggered by cellular stress responses. Recently, an increasing number of studies have implicated defects in Golgi functioning in human diseases such as cancer, neurodegenerative, and immunological disorders. Understanding the extraordinary characteristics of Golgi proteins is important for elucidating its associated intracellular signaling mechanisms and has important ramifications for human health. Therefore, analyzing the mechanisms by which the Golgi participates in disease pathogenesis may be useful for developing novel therapeutic strategies. This review articulates the structural features and abnormalities of the Golgi apparatus reported in various diseases and the suspected mechanisms underlying the Golgi-associated pathologies. Furthermore, we review the potential therapeutic strategies based on Golgi function.
Topics: Humans; Golgi Apparatus; Proteins; Protein Processing, Post-Translational; Homeostasis
PubMed: 36178581
DOI: 10.1007/s12272-022-01408-z -
Protoplasma Jul 2016Centrioles and centrosomes are found in almost all eukaryotic cells, where they are important for organising the microtubule cytoskeleton in both dividing and... (Review)
Review
Centrioles and centrosomes are found in almost all eukaryotic cells, where they are important for organising the microtubule cytoskeleton in both dividing and non-dividing cells. The spatial location of centrioles and centrosomes is tightly controlled and, in non-dividing cells, plays an important part in cell migration, ciliogenesis and immune cell functions. Here, we examine some of the ways that centrosomes are connected to other organelles and how this impacts on cilium formation, cell migration and immune cell function in metazoan cells.
Topics: Animals; Cell Movement; Cell Nucleus; Cell Polarity; Centrosome; Cilia; Golgi Apparatus; Humans
PubMed: 26319517
DOI: 10.1007/s00709-015-0883-5